The biological significance of non-enzymatic reaction of menadione with plasma thiols: enhancement of menadione-induced cytotoxicity to platelets by the presence of blood plasma

AbstractTo test the hypothesis that the non-enzymatic reaction of quinones with thiols in plasma can generate reactive oxygens (ROS), thereby leading to potentiated cellular toxicity, we have studied the effect of a representative quinone compound, menadione, on plasma isolated from rats. The experimental results are as follows: (1) menadione generated ROS via non-enzymatic reaction with protein thiols in plasma; (2) the presence of plasma increased menadione-induced cytotoxicity to platelets; (3) pretreatment of plasma with a thiol-depleting agent significantly suppressed menadione-induced ROS and cytotoxicity. These results suggest that the non-enzymatic reaction of menadione with plasma thiols could be an important process in quinone-induced cellular toxicity

Analysis of online parenting community posts on expanded newborn screening for metabolic disorders using topic modeling: a quantitative content analysis

Purpose As more newborns have received expanded newborn screening (NBS) for metabolic disorders, the overall number of false-positive results has increased. The purpose of this study was to explore the psychological impacts experienced by mothers related to the NBS process. Methods An online parenting community in Korea was selected, and questions regarding NBS were collected using web crawling for the period from October 2018 to August 2021. In total, 634 posts were analyzed. The collected unstructured text data were preprocessed, and keyword analysis, topic modeling, and visualization were performed. Results Of 1,057 words extracted from posts, the top keyword based on ‘term frequency-inverse document frequency’ values was “hypothyroidism,” followed by “discharge,” “close examination,” “thyroid-stimulating hormone levels,” and “jaundice.” The top keyword based on the simple frequency of appearance was “XXX hospital,” followed by “close examination,” “discharge,” “breastfeeding,” “hypothyroidism,” and “professor.” As a result of LDA topic modeling, posts related to inborn errors of metabolism (IEMs) were classified into four main themes: “confirmatory tests of IEMs,” “mother and newborn with thyroid function problems,” “retests of IEMs,” and “feeding related to IEMs.” Mothers experienced substantial frustration, stress, and anxiety when they received positive NBS results. Conclusion The online parenting community played an important role in acquiring and sharing information, as well as psychological support related to NBS in newborn mothers. Nurses can use this study’s findings to develop timely and evidence-based information for parents whose children receive positive NBS results to reduce the negative psychological impact

Clinical Comparison of the Auditory Steady-State Response with the Click Auditory Brainstem Response in Infants

ObjectivesOur goal was to determine the effectiveness of using the auditory steady state response (ASSR) as a measure of hearing thresholds in infants who are suspected of having significant hearing loss, as compared with using the click-auditory brainstem response (C-ABR).MethodsWe retrospectively analyzed the audiologic profiles of 76 infants (46 boys and 30 girls, a total of 151 ears) who ranged in age from 1 to 12 months (average age: 5.7 months). The auditory evaluations in 76 infants who were suspected of having hearing loss were done via the C-ABR and ASSR. In addition, for reference, the mean ASSR thresholds were compared to those of 39 ears of infants and 39 ears of adults with normal hearing at 0.5, 1, 2, and 4 kHz.ResultsThe highest correlation between the C-ABR and ASSR thresholds was observed at an average of 2-4 kHz (r=0.94). On comparison between the hearing of infants and adults at 0.5, 1, 2, and 4 kHz, the mean ASSR threshold in infants was 12, 7, 8, and 7 dB higher, respectively, than that in adults.ConclusionASSR testing may provide additional audiometric information for accurately predicting the hearing sensitivity, and this is essential for the management of infants with severe to profound hearing loss

Simple Quantification of Pentosidine in Human Urine and Plasma by High-Performance Liquid Chromatography

Pentosidine is an advanced glycation end-product (AGE) and fluorescent cross-link compound. A simple high-performance liquid chromatographic (HPLC) method was developed for the detection and quantification of pentosidine in human urine and plasma. The mobile phase used a gradient system to improve separation of pentosidine from endogenous peaks, and chromatograms were monitored by fluorescent detector set at excitation and emission wavelengths of 328 and 378 nm, respectively. The retention time for pentosidine was 24.3 min and the lower limits of quantification (LLOQ) in human urine and plasma were 1 nM. The intraday assay precisions (coefficients of variation) were generally low and found to be in the range of 5.19–7.49% and 4.96–8.78% for human urine and plasma, respectively. The corresponding values of the interday assay precisions were 9.45% and 4.27%. Accuracies (relative errors) ranged from 87.9% to 115%. Pentosidine was stable in a range of pH solutions, human urine, and plasma. In summary, this HPLC method can be applied in future preclinical and clinical evaluation of pentosidine in the diabetic patients

Therapeutic Effects of Holmium-166 Chitosan Complex in Rat Brain Tumor Model

This study examined the effectiveness of Holmium-166 (Ho-166) chitosan complex therapy for a malignant glioma. Cultured C6 glioma cells (100,000 in 5 µl) were injected into the caudate/putamen of 200 - 250 gram Wistar rats. Five days later, a Ho-166 chitosan complex was injected into the same site of the glioma injection. Four injection doses were administered: the control group received PBS 10 µl, group 1 received an injection of 100 µCi (10 µl), group 2 received an injection of 50 µCi (5 µl), and group 3 received an injection of 10 µCi (1 µl). The average tumor volume for each group was 1.385 mm3 for the control group, 0.036 mm3 for group 1, 0.104 mm3 for group 2, and 0.111 mm3 for group 3. Compared with the control group, the size of the tumors in groups 1, 2 and 3 was reduced by an average of 97.4%, 92.5% and 91.9%, respectively. The Kaplan-Meier survival curve of group 2 was the longest, followed by groups 3, group 1 and the control. The mean survival was 22.8, 59, 60, and 44.6 days for the control group and groups 3, 2 and 1, respectively. H-E staining revealed that group 2 yielded the best results in the destruction of the malignant glioma. TUNEL staining and immunohistochemical studies indicated apoptotic features. The Ho-166 chitosan complex proved to be effective in destroying the malignant glioma

Primary Malignant Teratoma with a Primitive Neuroectodermal Tumor Component in Thyroid Gland : A Case Report

Teratomas comprise the most common extragonadal germ cell tumors in childhood. Most teratomas involving the thyroid are benign and occur in children. However, the adult cases reported are mostly malignant and commonly arise in the thyroid. We report a case of a 31-yr-old female with a huge neck mass. Pathologic examination revealed it to be malignant teratoma composed of primitive neuroepithelial tissue with primitive neural tubes and loose myxoid to fibrous immature mesenchymal stroma. The patient underwent extensive evaluation of the thyroid gland with computed tomography (CT) scan and positron emission tomography (PET) scan, which revealed no evidence of metastatic disease. She underwent total thyroidectomy with bilateral modified radical neck dissection, intensive chemotherapy and radiotherapy. At 22-months of follow-up, the patient has remained euthyroid and showed no evidence of recurrence. This is the first case, to our knowledge, of malignant thyroid teratoma with a exuberant primitive neuroectodermal tumor component in Korea

Safety, efficacy, and response predictors of anticoagulation for the treatment of nonmalignant portal-vein thrombosis in patients with cirrhosis: a propensity score matching analysis

Background/AimsPortal-vein thrombosis (PVT) develops in 10-25% of cirrhotic patients and may aggravate portal hypertension. There are few data regarding the effects of anticoagulation on nonmalignant PVT in liver cirrhosis. The aim of this study was to elucidate the safety, efficacy, and predictors of response to anticoagulation therapy in cirrhotic patients.MethodsPatients with liver cirrhosis and nonmalignant PVT were identified by a hospital electronic medical record system (called BESTCARE). Patients with malignant PVT, Budd-Chiari syndrome, underlying primary hematologic disorders, or preexisting extrahepatic thrombosis were excluded from the analysis. Patients were divided into two groups (treatment and nontreatment), and propensity score matching analysis was performed to identify control patients. The sizes of the thrombus and spleen were evaluated using multidetector computed tomography.ResultsTwenty-eight patients were enrolled in this study between 2003 and 2014: 14 patients who received warfarin for nonmalignant PVT and 14 patients who received no anticoagulation. After 112 days of treatment, 11 patients exhibited significantly higher response rates (complete in 6 and partial in 5) compared to the control patients, with decreases in thrombus size of >30%. Compared to nonresponders, the 11 responders were older, and had a thinner spleen and fewer episodes of previous endoscopic variceal ligations, whereas pretreatment liver function and changes in prothrombin time after anticoagulation did not differ significantly between the two groups. Two patients died after warfarin therapy, but the causes of death were not related to anticoagulation.ConclusionsWarfarin can be safely administered to cirrhotic patients with nonmalignant PVT. The presence of preexisting portal hypertension is a predictor of nonresponse to anticoagulation

Efficient Cultivation Conditions for Human Limbal Epithelial Cells

To compare the stem niche in different culture conditions of limbal epithelial cells, the suspended human limbal epithelial cells (HLECs) were seeded on the 3T3-pretreated plates and the other suspended cells were plated on amniotic membranes (AMs) which were either cryo-preserved or freeze-dried. All were cultured for 10 to 12 days. Reverse transcription-polymerase chain reaction (RT-PCR) for ATP-binding casette, subfamily G, member 2 (ABCG2), p63, cytokeratin 12, and connexin 43 were performed in cultivated HLECs and their expression levels were compared. The mRNA expression of all markers examined showed no statistically significant differences between the cells on cryo-preserved and on freeze-dried AM. The expression of p63 and cytokeratin 12 in cultivated cells on AMs were significantly lower than those in 3T3-cocultured cells on RT-PCR and immunofluorescent staining. Cultivated HLECs on AMs showed reduced proliferation and differentiation while maintaining stem-property regardless of the preservative method of AM

Clinical Comparison of the Auditory Steady-State Response with the Click Auditory Brainstem Response in Infants

ObjectivesOur goal was to determine the effectiveness of using the auditory steady state response (ASSR) as a measure of hearing thresholds in infants who are suspected of having significant hearing loss, as compared with using the click-auditory brainstem response (C-ABR).MethodsWe retrospectively analyzed the audiologic profiles of 76 infants (46 boys and 30 girls, a total of 151 ears) who ranged in age from 1 to 12 months (average age: 5.7 months). The auditory evaluations in 76 infants who were suspected of having hearing loss were done via the C-ABR and ASSR. In addition, for reference, the mean ASSR thresholds were compared to those of 39 ears of infants and 39 ears of adults with normal hearing at 0.5, 1, 2, and 4 kHz.ResultsThe highest correlation between the C-ABR and ASSR thresholds was observed at an average of 2-4 kHz (r=0.94). On comparison between the hearing of infants and adults at 0.5, 1, 2, and 4 kHz, the mean ASSR threshold in infants was 12, 7, 8, and 7 dB higher, respectively, than that in adults.ConclusionASSR testing may provide additional audiometric information for accurately predicting the hearing sensitivity, and this is essential for the management of infants with severe to profound hearing loss

Synergistic effect of ERK inhibition on tetrandrine-induced apoptosis in A549 human lung carcinoma cells

Tetrandrine (TET), a bis-benzylisoquinoline alkaloid from the root of Stephania tetrandra, is known to have anti-tumor activity in various malignant neoplasms. However, the precise mechanism by which TET inhibits tumor cell growth remains to be elucidated. The present studies were performed to characterize the potential effects of TET on phosphoinositide 3-kinase/Akt and extracellular signal-regulated kinase (ERK) pathways since these signaling pathways are known to be responsible for cell growth and survival. TET suppressed cell proliferation and induced apoptosis in A549 human lung carcinoma cells. TET treatment resulted in a down-regulation of Akt and ERK phosphorylation in both time-/concentration-dependent manners. The inhibition of ERK using PD98059 synergistically enhanced the TET-induced apoptosis of A549 cells whereas the inhibition of Akt using LY294002 had a less significant effect. Taken together, our results suggest that TET: i) selectively inhibits the proliferation of lung cancer cells by blocking Akt activation and ii) increases apoptosis by inhibiting ERK. The treatment of lung cancers with TET may enhance the efficacy of chemotherapy and radiotherapy and increase the apoptotic potential of lung cancer cells